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Erschienen in: Hepatology International 4/2011

01.12.2011 | Original Article

Serum retinol binding protein 4 and clinical outcome in postoperative biliary atresia

verfasst von: Maneerat Chayanupatkul, Sittisak Honsawek, Voranush Chongsrisawat, Linda Vimolket, Yong Poovorawan

Erschienen in: Hepatology International | Ausgabe 4/2011

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Abstract

Background

Biliary atresia (BA), a chronic inflammatory disease of bile ducts, is characterized by the obliteration of bile flow. The aim of the present study was to investigate serum retinol binding protein 4 (RBP4) in postoperative BA patients and the association of RBP4 with clinical parameters and liver stiffness scores.

Methods

A number of forty-eight BA patients post Kasai operation and 24 controls were enrolled. None of the patients had undergone liver transplantation. BA patients were classified into two groups according to their serum total bilirubin (TB) levels (non-jaundice, TB < 2 mg/dl vs. jaundice, TB ≥ 2 mg/dl) and liver stiffness (insignificant fibrosis, liver stiffness <7 kPa vs. significant fibrosis, liver stiffness ≥7 kPa). Serum RBP4 levels were determined by enzyme-linked immunosorbent assay (ELISA). Liver stiffness scores were measured by FibroScan.

Results

BA patients had lower RBP4 levels (14.9 ± 1.0 vs. 18.7 ± 1.0 ng/ml, P = 0.02), but higher liver stiffness than controls (29.5 ± 3.3 vs. 5.0 ± 0.5 kPa, P < 0.001). Serum RBP4 levels were significantly decreased in BA patients with jaundice, compared with those without jaundice (9.5 ± 0.9 vs. 18.2 ± 1.2 ng/ml, P < 0.001). Moreover, BA patients with significant liver fibrosis displayed lower serum RBP4 than those with insignificant fibrosis (14.1 ± 1.2 vs. 21.2 ± 1.4 ng/ml, P = 0.02). Further analysis showed that serum RBP4 was strongly correlated with liver stiffness and serum albumin (r = −0.72, P < 0.001, and r = 0.65, P < 0.001, respectively). BA patients with portal hypertension (PH) had lower serum RBP4 than those without PH (12.8 ± 1.2 vs. 19.2 ± 1.7 ng/ml, P = 0.003).

Conclusion

Serum RBP4 levels decreased in BA patients compared with normal participants, and its levels declined significantly in patients with more severe disease. RBP4 may play a role in the pathogenesis of hepatic fibrosis and serve as a possible biomarker reflecting disease severity in postoperative BA patients.
Literatur
1.
Zurück zum Zitat Mckirnan PJ, Baker AJ, Kelly DA. The frequency and outcome of biliary atresia in the UK and Ireland. Lancet 2000;355:25–29CrossRef Mckirnan PJ, Baker AJ, Kelly DA. The frequency and outcome of biliary atresia in the UK and Ireland. Lancet 2000;355:25–29CrossRef
2.
Zurück zum Zitat Balistreri WF, Grand R, Hoofnagle JH, Suchy FJ, Ryckman FC, Perlmutter DH, et al. Biliary atresia: current concepts and research directions. Summary of symphosium. Hepatology 1996;23:1682–1692PubMedCrossRef Balistreri WF, Grand R, Hoofnagle JH, Suchy FJ, Ryckman FC, Perlmutter DH, et al. Biliary atresia: current concepts and research directions. Summary of symphosium. Hepatology 1996;23:1682–1692PubMedCrossRef
3.
Zurück zum Zitat Altman RP, Lilly JR, Greenfield J, Weinburg A, van Leeuwen K, Flanigan L. A multivariable risk factor analysis of the portoenterostomy (Kasai) procedure for biliary atresia: twenty-five years of experience from two centers. Ann Surg 1997;226:348–353PubMedCrossRef Altman RP, Lilly JR, Greenfield J, Weinburg A, van Leeuwen K, Flanigan L. A multivariable risk factor analysis of the portoenterostomy (Kasai) procedure for biliary atresia: twenty-five years of experience from two centers. Ann Surg 1997;226:348–353PubMedCrossRef
4.
Zurück zum Zitat A-Kader HH, Abdel-Hameed A, Al-Shabrawi M, Mohsen N, El-Karaksy H, Hassanein B, et al. Is biliary atresia an autoimmune disease? Eur J Gastroenterol Hepatol 2003;5:447CrossRef A-Kader HH, Abdel-Hameed A, Al-Shabrawi M, Mohsen N, El-Karaksy H, Hassanein B, et al. Is biliary atresia an autoimmune disease? Eur J Gastroenterol Hepatol 2003;5:447CrossRef
5.
Zurück zum Zitat Mark CL, Sokol RJ. Unraveling the pathogenesis and etiology of biliary atresia. Pediatr Res 2005;57:87R–94RCrossRef Mark CL, Sokol RJ. Unraveling the pathogenesis and etiology of biliary atresia. Pediatr Res 2005;57:87R–94RCrossRef
6.
Zurück zum Zitat Gressner OA, Gressner AM. Connective tissue growth factor: a fibrogenic master switch in fibrotic liver diseases. Liver Int 2008;28:1065–1079PubMedCrossRef Gressner OA, Gressner AM. Connective tissue growth factor: a fibrogenic master switch in fibrotic liver diseases. Liver Int 2008;28:1065–1079PubMedCrossRef
7.
Zurück zum Zitat Gressner AM, Weiskirchen R. Modern pathogenetic concepts of liver fibrosis suggest stellate cells and TGF-beta as major players and therapeutic targets. J Cell Mol Med 2006;10:76–99PubMedCrossRef Gressner AM, Weiskirchen R. Modern pathogenetic concepts of liver fibrosis suggest stellate cells and TGF-beta as major players and therapeutic targets. J Cell Mol Med 2006;10:76–99PubMedCrossRef
8.
Zurück zum Zitat Chuang JH, Wang PW, Tai MH. An adipocentric view of liver fibrosis and cirrhosis. Chang Gung Med J 2004;27:855–868PubMed Chuang JH, Wang PW, Tai MH. An adipocentric view of liver fibrosis and cirrhosis. Chang Gung Med J 2004;27:855–868PubMed
9.
Zurück zum Zitat Blaner WS. Retinol-binding protein: the serum transport protein for vitamin A. Endocr Rev 1989;10:308–316PubMedCrossRef Blaner WS. Retinol-binding protein: the serum transport protein for vitamin A. Endocr Rev 1989;10:308–316PubMedCrossRef
10.
Zurück zum Zitat Yang Q, Graham TE, Mody N, Preitner F, Peroni OD, Zabolotny JM, et al. Serum retinol binding protein 4 contributes to insulin resistance in obesity and type 2 diabetes. Nature 2005;436:356–362PubMedCrossRef Yang Q, Graham TE, Mody N, Preitner F, Peroni OD, Zabolotny JM, et al. Serum retinol binding protein 4 contributes to insulin resistance in obesity and type 2 diabetes. Nature 2005;436:356–362PubMedCrossRef
11.
Zurück zum Zitat Graham TE, Yang Q, Bluher M, Hammarstedt A, Ciaraldi TP, Henry RR, et al. Retinol-binding protein 4 and insulin resistance in lean, obese, and diabetic subjects. N Engl J Med 2006;354:2552–2563PubMedCrossRef Graham TE, Yang Q, Bluher M, Hammarstedt A, Ciaraldi TP, Henry RR, et al. Retinol-binding protein 4 and insulin resistance in lean, obese, and diabetic subjects. N Engl J Med 2006;354:2552–2563PubMedCrossRef
12.
Zurück zum Zitat Petta S, Camma C, Di Marco V, Alessi N, Barbaria F, Cabibi D, et al. Retinol-binding protein 4: a new marker of virus-induced steatosis in patients infected with hepatitis C virus genotype 1. Hepatology 2008;48:28–37PubMedCrossRef Petta S, Camma C, Di Marco V, Alessi N, Barbaria F, Cabibi D, et al. Retinol-binding protein 4: a new marker of virus-induced steatosis in patients infected with hepatitis C virus genotype 1. Hepatology 2008;48:28–37PubMedCrossRef
13.
Zurück zum Zitat Seo JA, Kim NH, Park SY, Kim HY, Ryu OH, Lee KW, et al. Serum retinol-binding protein 4 levels are elevated in non-alcoholic fatty liver disease. Clin Endocrinol 2008;68:555–560CrossRef Seo JA, Kim NH, Park SY, Kim HY, Ryu OH, Lee KW, et al. Serum retinol-binding protein 4 levels are elevated in non-alcoholic fatty liver disease. Clin Endocrinol 2008;68:555–560CrossRef
14.
Zurück zum Zitat Bahr MJ, Boeker KHW, Manns MP, Tietge UJF. Decreased hepatic RBP4 secretion is correlated with reduced hepatic glucose production but is not associated with insulin resistance in patients with liver cirrhosis. Clin Endocrinol 2009;70:60–65CrossRef Bahr MJ, Boeker KHW, Manns MP, Tietge UJF. Decreased hepatic RBP4 secretion is correlated with reduced hepatic glucose production but is not associated with insulin resistance in patients with liver cirrhosis. Clin Endocrinol 2009;70:60–65CrossRef
15.
Zurück zum Zitat Yagmur E, Weiskirchen R, Gressner AM, Trautwein C, Tacke F. Insulin resistance in liver cirrhosis is not associated with the circulating retinol-binding protein 4. Diabetes Care 2007;30:1168–1172PubMedCrossRef Yagmur E, Weiskirchen R, Gressner AM, Trautwein C, Tacke F. Insulin resistance in liver cirrhosis is not associated with the circulating retinol-binding protein 4. Diabetes Care 2007;30:1168–1172PubMedCrossRef
16.
Zurück zum Zitat Schina M, Koskinas J, Tiniakos D, Hadziyannis E, Savvas S, Karamanos B, et al. Circulating and liver tissue levels of retinol-binding protein 4 in non-alcoholic fatty liver disease. Hepatol Res 2009;39:972–978PubMedCrossRef Schina M, Koskinas J, Tiniakos D, Hadziyannis E, Savvas S, Karamanos B, et al. Circulating and liver tissue levels of retinol-binding protein 4 in non-alcoholic fatty liver disease. Hepatol Res 2009;39:972–978PubMedCrossRef
17.
Zurück zum Zitat Nobili V, Alkhouri N, Alisi A, Ottino S, Lopez R, Manco M, et al. Retinol-binding protein 4: promising circulating marker of liver damage in pediatric nonalcoholic fatty liver disease. Clin Gastroenterol Hepatol 2009;7:575–579PubMedCrossRef Nobili V, Alkhouri N, Alisi A, Ottino S, Lopez R, Manco M, et al. Retinol-binding protein 4: promising circulating marker of liver damage in pediatric nonalcoholic fatty liver disease. Clin Gastroenterol Hepatol 2009;7:575–579PubMedCrossRef
18.
Zurück zum Zitat Alkhouri N, Lopez R, Berk M, Feldstein AE. Serum retinol-binding protein 4 levels in patients with nonalcoholic fatty liver disease. J Clin Gastroenterol 2009;43:985–989PubMedCrossRef Alkhouri N, Lopez R, Berk M, Feldstein AE. Serum retinol-binding protein 4 levels in patients with nonalcoholic fatty liver disease. J Clin Gastroenterol 2009;43:985–989PubMedCrossRef
19.
Zurück zum Zitat Tacke F, Weiskirchen R, Trautwein C. Liver function critically determines serum retinol-binding protein 4 (RBP4) levels in patients with chronic liver disease and cirrhosis. Hepatology 2008;48:1724–1725PubMedCrossRef Tacke F, Weiskirchen R, Trautwein C. Liver function critically determines serum retinol-binding protein 4 (RBP4) levels in patients with chronic liver disease and cirrhosis. Hepatology 2008;48:1724–1725PubMedCrossRef
20.
Zurück zum Zitat Huang JF, Dai CY, Yu ML, Shin SJ, Hsieh MY, Huang CF, et al. Serum retinol-binding protein 4 is inversely correlated with disease severity of chronic hepatitis C. J Hepatol 2009;50:471–478PubMedCrossRef Huang JF, Dai CY, Yu ML, Shin SJ, Hsieh MY, Huang CF, et al. Serum retinol-binding protein 4 is inversely correlated with disease severity of chronic hepatitis C. J Hepatol 2009;50:471–478PubMedCrossRef
21.
Zurück zum Zitat Honsawek S, Chayanupatkul M, Chongsrisawat V, Vejchapipat P, Poovorawan Y. Increased osteopontin and liver stiffness measurement by transient elastography in biliary atresia. World J Gastroenterol 2010;16:5467–547PubMedCrossRef Honsawek S, Chayanupatkul M, Chongsrisawat V, Vejchapipat P, Poovorawan Y. Increased osteopontin and liver stiffness measurement by transient elastography in biliary atresia. World J Gastroenterol 2010;16:5467–547PubMedCrossRef
22.
Zurück zum Zitat Honsawek S, Chaiwatanarat T, Chongsrisawat V, Thawornsuk N, Vejchapipat P, Poovorawan Y. Circulating leptin levels and bone mineral density in children with biliary atresia. Acta Paediatr 2008;97:206–211PubMedCrossRef Honsawek S, Chaiwatanarat T, Chongsrisawat V, Thawornsuk N, Vejchapipat P, Poovorawan Y. Circulating leptin levels and bone mineral density in children with biliary atresia. Acta Paediatr 2008;97:206–211PubMedCrossRef
23.
Zurück zum Zitat Honsawek S, Chongsrisawat V, Vejchapipat P, Thawornsuk N, Poovorawan Y. High levels of serum basic fibroblast growth factor in children with biliary atresia. Hepatogastroenterology 2008;55:1184–1188PubMed Honsawek S, Chongsrisawat V, Vejchapipat P, Thawornsuk N, Poovorawan Y. High levels of serum basic fibroblast growth factor in children with biliary atresia. Hepatogastroenterology 2008;55:1184–1188PubMed
24.
Zurück zum Zitat Wai CT, Greenson JK, Fontana RJ, Kalbfleisch JD, Marrero JA, Conjeevaram HS, et al. A simple noninvasive index can predict both significant fibrosis and cirrhosis in patients with chronic hepatitis C. Hepatology 2003;38:518–526PubMedCrossRef Wai CT, Greenson JK, Fontana RJ, Kalbfleisch JD, Marrero JA, Conjeevaram HS, et al. A simple noninvasive index can predict both significant fibrosis and cirrhosis in patients with chronic hepatitis C. Hepatology 2003;38:518–526PubMedCrossRef
25.
Zurück zum Zitat Chang HK, Park YJ, Koh H, Kim SM, Chung KS, Oh JT, et al. Hepatic fibrosis scan for liver stiffness score measurement: a useful preendoscopic screening test for the detection of varices in postoperative patients with biliary atresia. J Pediatr Gastroenterol Nutr 2009;49:323–328PubMedCrossRef Chang HK, Park YJ, Koh H, Kim SM, Chung KS, Oh JT, et al. Hepatic fibrosis scan for liver stiffness score measurement: a useful preendoscopic screening test for the detection of varices in postoperative patients with biliary atresia. J Pediatr Gastroenterol Nutr 2009;49:323–328PubMedCrossRef
26.
Zurück zum Zitat Castara L, Vergniol J, Foucher J, Le Bail B, Chanteloup E, Haaser M, et al. Prospective comparison of transient elastography, Fibrotest, APRI, and liver fibrosis for the assessment of fibrosis in chronic hepatitis C. Gastroenterology 2005;128:343–350CrossRef Castara L, Vergniol J, Foucher J, Le Bail B, Chanteloup E, Haaser M, et al. Prospective comparison of transient elastography, Fibrotest, APRI, and liver fibrosis for the assessment of fibrosis in chronic hepatitis C. Gastroenterology 2005;128:343–350CrossRef
27.
Zurück zum Zitat Bluher M, Tonjes A, Stumvoll M. Dose retinol-binding protein 4 cause or reflect fatty liver disease? Hepatology 2008;48:4–6PubMedCrossRef Bluher M, Tonjes A, Stumvoll M. Dose retinol-binding protein 4 cause or reflect fatty liver disease? Hepatology 2008;48:4–6PubMedCrossRef
28.
Zurück zum Zitat Ohata M, Lin M, Satre M, Tsukamoto H. Diminished retinoic acid signaling in hepatic stellate cells in cholestatic liver fibrosis. Am J Physiol 1997;272:G589–G596PubMed Ohata M, Lin M, Satre M, Tsukamoto H. Diminished retinoic acid signaling in hepatic stellate cells in cholestatic liver fibrosis. Am J Physiol 1997;272:G589–G596PubMed
29.
Zurück zum Zitat Wang L, Attard FA, Tankersley LR, Potter JJ, Mezey E. Effect of retinoic acid on the enhancing effect of acetaldehyde on mouse type I collagen expression. Arch Biochem Biophys 2000;376:191–198PubMedCrossRef Wang L, Attard FA, Tankersley LR, Potter JJ, Mezey E. Effect of retinoic acid on the enhancing effect of acetaldehyde on mouse type I collagen expression. Arch Biochem Biophys 2000;376:191–198PubMedCrossRef
30.
Zurück zum Zitat Frey SK, Nagl B, Henze A, Raila J, Schlosser B, Berg T, et al. Isoforms of retinol binding protein 4 (RBP4) are increased in chronic diseases of the kidney but not of the liver. Lipids Health Dis 2008;7:29PubMedCrossRef Frey SK, Nagl B, Henze A, Raila J, Schlosser B, Berg T, et al. Isoforms of retinol binding protein 4 (RBP4) are increased in chronic diseases of the kidney but not of the liver. Lipids Health Dis 2008;7:29PubMedCrossRef
31.
Zurück zum Zitat Quadro L, Blaner WS, Salchow DJ, Vogel S, Piantedosi R, Gouras P, et al. Impaired retinol function and vitamin A availability in mice lacking retinol-binding protein. EMBO J 1999;18:4444–4633CrossRef Quadro L, Blaner WS, Salchow DJ, Vogel S, Piantedosi R, Gouras P, et al. Impaired retinol function and vitamin A availability in mice lacking retinol-binding protein. EMBO J 1999;18:4444–4633CrossRef
32.
Zurück zum Zitat Foucher J, Chanteloup E, Vergniol J. Diagnosis of cirrhosis by transient elastography (FibroScan): a prospective study. Gut 2006;55:403–408PubMedCrossRef Foucher J, Chanteloup E, Vergniol J. Diagnosis of cirrhosis by transient elastography (FibroScan): a prospective study. Gut 2006;55:403–408PubMedCrossRef
33.
Zurück zum Zitat Cengiz C, Ardicoglu Y, Bulut S, Boyacioglu S. Serum retinol-binding protein 4 in patients with nonalcoholic fatty liver disease: dose it have a significant impact on pathogenesis. Eur J Gastroenterol Hepatol 2010;22:813–819PubMedCrossRef Cengiz C, Ardicoglu Y, Bulut S, Boyacioglu S. Serum retinol-binding protein 4 in patients with nonalcoholic fatty liver disease: dose it have a significant impact on pathogenesis. Eur J Gastroenterol Hepatol 2010;22:813–819PubMedCrossRef
Metadaten
Titel
Serum retinol binding protein 4 and clinical outcome in postoperative biliary atresia
verfasst von
Maneerat Chayanupatkul
Sittisak Honsawek
Voranush Chongsrisawat
Linda Vimolket
Yong Poovorawan
Publikationsdatum
01.12.2011
Verlag
Springer-Verlag
Erschienen in
Hepatology International / Ausgabe 4/2011
Print ISSN: 1936-0533
Elektronische ISSN: 1936-0541
DOI
https://doi.org/10.1007/s12072-011-9262-2

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